TR4 worsen urosepsis by regulating GSDMD.

BACKGROUND: Urosepsis is a life-threatening organ disease in which pathogenic microorganisms in the urine enter the blood through the vessels, causing an imbalance in the immune response to infection. The aim of this study was to elucidate the role of testicular orphan receptor 4 (TR4) in urosepsis. METHODS: The role of TR4 in the progression and prognosis of urosepsis was confirmed by analyzing data from online databases and clinical human samples. To mimic urosepsis, we injected E. coli bacteria into the renal pelvis of mice to create a urosepsis model. Hematoxylin and eosin staining was used to observe histopathological changes in urosepsis. The effects of the upregulation or downregulation of TR4 on macrophage pyroptosis were verified in vitro. Chromatin immunoprecipitation assay was used to verify the effect of TR4 on Gasdermin D (GSDMD) transcription. RESULTS: TR4 was more highly expressed in the nonsurviving group than in the surviving group. Furthermore, overexpressing TR4 promoted inflammatory cytokine expression, and knocking down TR4 attenuated inflammatory cytokine expression. Mechanistically, TR4 promoted pyroptosis by regulating the expression of GSDMD in urosepsis. Furthermore, we also found that TR4 knockdown protected mice from urosepsis induced by the E. coli. CONCLUSIONS: TR4 functions as a key regulator of urosepsis by mediating pyroptosis, which regulates GSDMD expression. Targeting TR4 may be a potential strategy for urosepsis treatment.

Tribological behavior and in vitro biocompatibility of powder metallurgical Ti-15Mo/HA composite for bone repair.

Ti-15Mo/HA composite was prepared by powder metallurgy, and the influence of Hydroxyapatite (HA) on the microstructure, tribological behavior and in vitro biocompatibility was studied by comparison with TC4. The results show that the Ti-15Mo/HA composite consists of increased α-Ti, decreased ß-Ti and a variety of ceramic phases (CaTiO3, Ca3(PO4)2, CaO, etc.) with the increase of HA content. The friction coefficient and wear rate of Ti-15Mo/HA composite is apparently lower than those of TC4 due to solid solution strengthening of Mo in Ti and dispersion strengthening of ceramic phases. Ti-15Mo/5HA displays more excellent wear resistance than the other composite. TC4 alloy is dominated by adhesive wear, however, Ti-15Mo alloy is a combination of adhesive wear and abrasive wear. Ti-15Mo/HA composite is mainly subjected to abrasive wear, together with adhesive wear. The viability and the number of mouse osteoblasts in Ti-15Mo/5HA extract are higher than that of Ti-15Mo. The morphology of the osteoblasts is clear and full, and the growth and proliferation are satisfactory with the increased cell pseudopodia with the culture time. The Ti-15Mo/HA composite displays good wear resistance and biocompatibility, and accordingly has a potential application in bone repair materials.

Comprehensive analysis of subtypes and risk model based on complement system associated genes in ccRCC.

BACKGROUND: Immune therapy is widely used in treating clear cell renal cell carcinoma (ccRCC), yet identifying patient subgroups that are expected to response remains challenging. As complement system can mediate immune effects, including the progression of tumors, a correlation between complement system and immune therapy may exist. METHODS: Based on 11 complement system associated genes (CSAGs) identified from The Cancer Genome Atlas (TCGA), we performed unsupervised clustering and classified the tumors into two different complement system (CS) patterns. The clinical significance, tumor microenvironment (TME), functional enrichment, and immune infiltration were further analyzed. A novel scoring system named CSscore was developed based on the expression levels of the 11 CSAGs. RESULTS: Two distinct CS patterns were identified, classified as Cluster1 and Cluster2, and Cluster1 showed poor clinical outcome. Further analysis of functional enrichment, immune cell infiltration, and genetic variation revealed that Cluster1 had high infiltration of TME immune cells, but also exhibited high immune escape. The novel prognostic model, CSscore could act as an independent prognostic factor and effectively predict patients' prognosis and distinguish the therapeutic efficacy of different immune treatment strategies. The pan-cancer analysis of the CSscore indicates its potential to be further generalized to other types of cancer. CONCLUSIONS: Two distinct CS patterns were identified and were further analyzed in terms of infiltration of TME immune cells and immune escape, providing potential explanations for the impact on prognosis of ccRCC. Our CSscore prognostic model may offer a novel perspective in the management of ccRCC patients, and potentially other types of cancer as well.

HIF1A-repressed PUS10 regulates NUDC/Cofilin1 dependent renal cell carcinoma migration by promoting the maturation of miR-194-5p.

BACKGROUND: Renal cell carcinoma (RCC) is characterized by a high rate of distant metastasis, which leads to poor prognosis in patients with advanced RCC. PUS10 has been recognized as a member of the pseudouridine synthase family, and recently other functions beyond the synthesis of the RNA modification have been uncovered. However, little is known about its role in diseases such as cancer. METHODS: RT-qPCR, western blot and immunohistochemistry were used to measure the expression of PUS10 in RCC tissues. Transwell assay, wound healing assay, and in vivo metastasis model were conducted to determine the function of PUS10 in RCC progression. MicroRNA sequencing and GEO database were used to screen for the downstream microRNAs of PUS10. RNA immunoprecipitation, dual luciferase reporter assay, immunostaining, and rescue experiments were employed to establish the PUS10/miR-194-5p/nuclear distribution protein C(NUDC)/Cofilin1 axis in RCC migration. Chromatin immunoprecipitation and dual luciferase reporter assay were used to verify its upstream transcriptional regulator. RESULTS: The expression of PUS10 was significantly decreased in RCC tissues, and low expression predicted poor prognosis. In vitro and in vivo experiments showed that PUS10 suppressed RCC migration, which, however, was independent of its classical pseudouridine catalytic function. Mechanically, PUS10 promoted the maturation of miR-194-5p, which sequentially inhibited RCC migration via disrupting NUDC-dependent cytoskeleton. Furthermore, hypoxia and HIF-1 A were found involved in the downregulation of PUS10. CONCLUSION: We unraveled PUS10 restrained RCC migration via the PUS10/miR-194-5p/NUDC/Cofilin1 pathway, which independent of its classical catalytic function. Furthermore, a linkage between the critical tumor microenvironment hallmark with malfunction of the forementioned metastasis inhibition mechanism was presented, as demonstrated by repressed expression of PUS10 due to hypoxia and HIF-1A.

Methacrylate bonded covalent organic framework monolithic column online coupling with high-performance liquid chromatography for analysis of trace estrogens in food.

Covalent organic frameworks (COFs) are a burgeoning class of crystalline porous materials with unique properties and have been considered as a promising functional extraction medium in sample pretreatment. In this study, a new methacrylate-bonded COF (TpTh-MA) was well designed and synthesized via the aldehyde-amine condensation reaction, and the TpTh-MA was incorporated into poly (ethylene dimethacrylate) porous monolith by a facile polymerization reaction inside capillary to prepare a novel TpTh-MA monolithic column. The fabricated TpTh-MA monolithic column was characterized with scanning electron microscope, Fourier transform infrared spectrometer, X-ray diffraction, and N2 adsorption-desorption experiments. Then, the homogeneous porous structure, good permeability and high mechanical stability of TpTh-MA monolithic column was used as separation and enrichment media of capillary microextraction, which was coupled with high-performance liquid chromatography fluorescence detection for online enrichment and analysis of trace estrogens. The main experimental parameters influencing the extraction efficiency were systematically investigated. The adsorption mechanism for three estrogens was also explored and discussed based on hydrophobic effect, π-π affinity and hydrogen bonding interaction, which contributed to its strong recognition affinity to target compounds. The enrichment factors of the TpTh-MA monolithic column micro extraction method for the three estrogens were 107-114, indicating a significant preconcentration ability. Under optimal conditions, a new online analysis method was developed and exhibited good sensitivity and wide linearity range of 0.25-100.0 µg·L-1 with a coefficient of determination (R2) higher than 0.9990 and a low limit of detection with 0.05-0.07 µg·L-1. The method was successfully applied for online analysis of three estrogens of milk and shrimp samples and the recoveries obtained from spiking experiments were in range of 81.4-113% and 77.9-111%, with the relative standard deviations of 2.6-7.9% and 2.1-8.3% (n = 5), respectively. The results revealed the great potential for the application of the COFs-bonded monolithic column in the field of sample pretreatment.

Exosomes in Genitourinary Cancers: Emerging Mediators of Drug Resistance and Promising Biomarkers.

Drug resistance presents a major obstacle in the treatment of genitourinary cancers. Exosomes as the medium of intercellular communication serve important biological functions and play essential roles in pathological processes, including drug response. Through the transfer of bioactive cargoes, exosomes can modulate drug resistance via multiple mechanisms. This review attempts to elucidate the mechanisms of exosomal cargoes with reference to tumor drug resistance, their role in genitourinary cancers, and their potential clinical applications as candidate biomarkers in liquid biopsy.

Exosome-derived circTFDP2 promotes prostate cancer progression by preventing PARP1 from caspase-3-dependent cleavage.

BACKGROUND: Circular RNAs (circRNAs) have been reported to play a significant role in tumorigenesis. However, the detailed function of circRNA in prostate cancer (PCa) is still largely unknown. METHODS: We quantified circTFDP2 expression in PCa tissues and adjacent normal tissues using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Colony formation, Cell Counting Kit-8 (CCK-8), flow cytometry, transwell, and in vivo progression and metastasis assays were applied to reveal the proliferation and metastatic abilities of circTFDP2 in PCa cells. Mass spectrometry, RNA pulldown, RNA-immunoprecipitation (RIP), western blotting and immunofluorescence were used for the mechanistic studies. qRT-PCR and RIP assays were used to explore the regulatory role of eIF4A3 in the biogenesis of circTFDP2. Finally, functional assays showed the effect of circTFDP2-containing exosomes on PCa cell progression. RESULTS: circTFDP2 was upregulated in PCa tissues compared with adjacent normal tissues. Furthermore, high circTFDP2 expression was positively correlated with the Gleason score. Functionally, circTFDP2 promoted PCa cell proliferation and metastasis both in vivo and in vitro. Mechanistically, circTFDP2 interacted with poly(ADP-ribose) polymerase 1 (PARP1) protein in its DNA-binding domain to prevent it from active caspase-3-dependent cleavage, and finally relieved PCa cells from DNA damage. In addition, RNA-binding protein eIF4A3 can interact with the flanking region of circTFDP2 and promote the biogenesis of circTFDP2. Moreover, exosome-derived circTFDP2 promoted PCa cell progression. CONCLUSIONS: In general, our study demonstrated that circTFDP2 promoted PCa cell progression through the PARP1/DNA damage axis, which may be a promising therapeutic target for PCa.

circPHF16 suppresses prostate cancer metastasis via modulating miR-581/RNF128/Wnt/ß-catenin pathway.

Circular RNAs (circRNAs) have been recognized as important regulators in tumorigenesis. However, the specific role of circRNAs in prostate cancer is still largely unknown. Here, we identified that circPHF16 was downregulated in prostate cancer (PCa) tissues compared with normal tissues. Functionally, circPHF16 restrained prostate cancer metastasis both in vivo and in vitro. Mechanistically, circPHF16 directly interacted with miR-581, leading to the downregulation of ring finger protein 128 (RNF128) and inhibiting the metastatic ability of PCa. Furthermore, circPHF16-dependent upregulation of RNF128 inactivated Wnt/ß-catenin signaling. In total, our findings revealed that circPHF16 suppressed prostate cancer metastasis through the circPHF16/miR-581/Wnt/ß-catenin pathways.

Adding fuel to the fire: The lipid droplet and its associated proteins in cancer progression.

A lipid droplet (LD) is an organelle that consists of a phospholipid monolayer and a neutral lipid core, with proteins embedded in or attached to its surface. Until recently, cancers had long been regarded as genetic disorders with the abnormal activation of oncogenes and inactivation of tumor suppressor genes before their quality of a metabolic disorder began to be recognized. The last decade has witnessed the recognition of several metabolic characteristics of cancer cells, among which one is the accumulation of lipid droplets; therefore, attention has been given to exploring the role of LDs in carcinomas. In addition, there has been a remarkable expansion in understanding the complexity of LD's function in cellular homeostasis, including but not limited to energy supply, endoplasmic reticulum (ER) stress and oxidative stress management, or lipotoxicity alleviation. Thus, lipid droplet-associated proteins, which to a great extent determine the dynamics of a lipid droplet, have attracted the interest of numerous cancer researchers and their potential as cancer diagnostic biomarkers and therapeutic targets has been affirmed by emerging evidence. In this review, we systematically summarize the critical role of LDs in cancer and then focus on four categories of lipid droplet-associated proteins having the most direct influence on LD biosynthesis (diacylglycerol acyltransferase 1 (DGAT1) and diacylglycerol acyltransferase 2 (DGAT2)), degradation (adipose triglyceride lipase (ATGL)), and two renowned protein families on the LD surface (perilipins and cell death-inducing DNA fragmentation factor alpha-like effectors (CIDEs)). In this way, we aim to highlight their important role in tumor progression and their potential in clinical applications.

METTL1 drives tumor progression of bladder cancer via degrading ATF3 mRNA in an m7G-modified miR-760-dependent manner.

7-methylguanosine (m7G) modification is recently found to conservatively exist in RNA internal position besides mRNA caps and mediates the various RNA metabolisms. As the core confirmed transmethylase of m7G modification, METTL1 has been reported in certain human cancers. However, the role of internal m7G at miRNAs and its core writer METTL1 in bladder cancer (BCa) remains to be elucidated. Here, we demonstrated that METTL1 was indispensable for BCa proliferation and metastasis in vitro and in vivo. By combining miRNA sequencing, m7G methylated RNA immunoprecipitation (MeRIP) and RIP, we identified METTL1 promoted the processing of miR-760 in an m7G-dependent manner. Transcription sequencing suggested that METTL1 indirectly degrades tumor suppressor ATF3 mRNA mediated by miR-760. Together, we concluded a regulatory axis composed of METTL1/m7G/miR-760/ATF3 in regulating BCa progression and provided potential therapeutic targets for BCa.

Nitroxoline suppresses metastasis in bladder cancer via EGR1/circNDRG1/miR-520h/smad7/EMT signaling pathway.

Bladder cancer is one of the most common and deadly cancer worldwide. Current chemotherapy has shown limited efficacy in improving outcomes for patients. Nitroxoline, an old and widely used oral antibiotic, which was known to treat for urinary tract infection for decades. Recent studies suggested that nitroxoline suppressed the tumor progression and metastasis, especially in bladder cancer. However, the underlying mechanism for anti-tumor activity of nitroxoline remains unclear. Methods: CircRNA microarray was used to explore the nitroxoline-mediated circRNA expression profile of bladder cancer lines. Transwell and wound-healing assay were applied to evaluate the capacity of metastasis. ChIP assay was chosen to prove the binding of promotor and transcription factor. RNA-pulldown assay was performed to explore the sponge of circRNA and microRNA. Results: We first identified the circNDRG1 (has_circ_0085656) as a novel candidate circRNA. Transwell and wound-healing assay demonstrated that circNDRG1 inhibited the metastasis of bladder cancer. ChIP assay showed that circNDRG1 was regulated by the transcription factor EGR1 by binding the promotor of host gene NDRG1. RNA-pulldown assay proved that circNDRG1 sponged miR-520h leading to the overexpression of smad7, which was a negative regulatory protein of EMT. Conclusions: Our research revealed that nitroxoline may suppress metastasis in bladder cancer via EGR1/circNDRG1/miR-520h/smad7/EMT signaling pathway.

circPDE5A regulates prostate cancer metastasis via controlling WTAP-dependent N6-methyladenisine methylation of EIF3C mRNA.

BACKGROUND: Circular RNA (circRNA) is a novel class noncoding RNA (ncRNA) that plays a critical role in various cancers, including prostate cancer (PCa). However, the clinical significance, biological function, and molecular mechanisms of circRNAs in prostate cancer remain to be elucidated. METHODS: A circRNA array was performed to identified the differentially expressed circRNAs. circPDE5A was identified as a novel circRNA which downregulated in clinical samples. Functionally, the in vitro and in vivo assays were applied to explore the role of circPDE5A in PCa metastasis. Mechanistically, the interaction between circPDE5A and WTAP was verified using RNA pulldown followed by mass spectrometry, RNA Immunoprecipitation (RIP) assays. m6A methylated RNA immunoprecipitation sequencing (MeRIP-seq) was then used to identified the downstream target of circPDE5A. Chromatin immunoprecipitation assay (ChIP) and dual-luciferase reporter assay were used to identified transcriptional factor which regulated circPDE5A expression. RESULTS: circPDE5A was identified downregulated in PCa tissues compared to adjacent normal tissue and was negatively correlated with gleason score of PCa patients. circPDE5A inhibits PCa cells migration and invasion both in vitro and in vivo. circPDE5A blocks the WTAP-dependent N6-methyladenisine (m6A) methylation of eukaryotic translation initiation factor 3c (EIF3C) mRNA by forming the circPDE5A-WTAP complex, and finally disrupts the translation of EIF3C. Moreover, the circPDE5A-dependent decrease in EIF3C expression inactivates the MAPK pathway and then restrains PCa progression. CONCLUSIONS: Our findings demonstrate that FOXO4-mediated upregulation of circPDE5A controls PCa metastasis via the circPDE5A-WTAP-EIF3C-MAPK signaling pathway and could serve as a potential therapeutic targer for PCa.

N6-methyladenosine-modified TRAF1 promotes sunitinib resistance by regulating apoptosis and angiogenesis in a METTL14-dependent manner in renal cell carcinoma.

BACKGROUND: Sunitinib resistance can be classified into primary and secondary resistance. While accumulating research has indicated several underlying factors contributing to sunitinib resistance, the precise mechanisms in renal cell carcinoma are still unclear. METHODS: RNA sequencing and m6A sequencing were used to screen for functional genes involved in sunitinib resistance. In vitro and in vivo experiments were carried out and patient samples and clinical information were obtained for clinical analysis. RESULTS: We identified a tumor necrosis factor receptor-associated factor, TRAF1, that was significantly increased in sunitinib-resistant cells, resistant cell-derived xenograft (CDX-R) models and clinical patients with sunitinib resistance. Silencing TRAF1 increased sunitinib-induced apoptotic and antiangiogenic effects. Mechanistically, the upregulated level of TRAF1 in sunitinib-resistant cells was derived from increased TRAF1 RNA stability, which was caused by an increased level of N6-methyladenosine (m6A) in a METTL14-dependent manner. Moreover, in vivo adeno-associated virus 9 (AAV9) -mediated transduction of TRAF1 suppressed the sunitinib-induced apoptotic and antiangiogenic effects in the CDX models, whereas knockdown of TRAF1 effectively resensitized the sunitinib-resistant CDXs to sunitinib treatment. CONCLUSIONS: Overexpression of TRAF1 promotes sunitinib resistance by modulating apoptotic and angiogenic pathways in a METTL14-dependent manner. Targeting TRAF1 and its pathways may be a novel pharmaceutical intervention for sunitinib-treated patients.

Simultaneous Enhancement of the Long-Wavelength NIR-II Brightness and Photothermal Performance of Semiconducting Polymer Nanoparticles.

Theranostic agents with fluorescence in the second near-infrared (NIR-II) window, especially in its long-wavelength region, and NIR-II-excitable photothermal effect is promising but challenging in tumor diagnosis and therapy. Here, we report a simple but effective strategy to develop semiconducting polymer nanoparticles-based theranostic agents (PBQx NPs) and demonstrate their applications for long-wavelength NIR-II fluorescence imaging beyond 1400 nm and photothermal therapy (PTT) of tumors upon excitation at 1064 nm. Both experimental results and theory calculations show that the brightness and photothermal performance of PBQx NPs can be simultaneously improved by simply increasing the repeating unit number of semiconducting polymers. For example, PBQ45 NPs have 5-fold higher brightness than PBQ5 NPs and 6.7-fold higher photothermal effect (based on PCE × Îµ) than PBQ3 NPs, and exhibit promising applications in long-wavelength NIR-II fluorescence abdomen imaging, image-guided tumor resection, and image-guided PTT. This study demonstrates the effectiveness and importance of repeating unit numbers in regulating the theranostic performance, which has not received enough attention before.

ß-Ketoenamine-linked covalent organic framework absorbent for online micro-solid phase extraction of trace levels bisphenols in plastic samples.

Covalent organic frameworks with tunable porous crystallinity and outstanding stability have exhibited fascinating pretreatment performance as ideal extraction media. Herein, the ß-ketoenamine-linked TpPa-1 synthesized by 1,3,5-triformylphloroglucinol and paraphenylenediamine was employed as the absorbent for online micro-solid phase extraction of trace bisphenols combined with high-performance liquid chromatography detection. A series of characterizations indicated that the TpPa-1 possessed large surface areas, high stability, and hydrophobicity. The main experimental parameters affecting the extraction efficiency were optimized in detail. Compared with four commercial sorbents, the TpPa-1 exhibited superior enrichment capacity for extracting bisphenols. Under the optimum conditions, the established method demonstrated a wide linear range and high sensitivity with the limit of detection ranging from 0.05-0.06 µg/L. Furthermore, the developed method was successfully applied to determine bisphenols in plastic samples. Bisphenol A was actually detected in a transparent box with a concentration of 0.31 µg/g, and the recoveries of the four bisphenols in the plastic samples were 80.5-116% with the relative standard deviation less than 9.2%. Such performance was attributed to recognition affinity, including the π-π affinity, hydrophobic effect, and hydrogen bond. These results demonstrated that TpPa-1 possessed great potential to be an excellent pretreatment medium for online separation and analysis of trace analytes in complex samples.

METTL14-mediated Lnc-LSG1 m6A modification inhibits clear cell renal cell carcinoma metastasis via regulating ESRP2 ubiquitination.

Clear cell renal cell carcinoma (ccRCC) is the most lethal urological cancer and is characterized by a high rate of metastasis and relapse. N6-Methyladenosine (m6A) is implicated in various stages of cancer development. However, a thorough understanding of m6A-modified lncRNAs in ccRCC is lacking. The results showed that METTL14 had decreased expression in ccRCC tissues. In addition, the expression of METTL14 was negatively correlated to the prognosis, stage, and ccRCC tumor grade. The silencing of METTL14 was shown to significantly increase metastasis in vitro and in vivo. High-throughput methylated RNA immunoprecipitation sequencing (MeRIP-seq) showed that the m6A levels of Lnc-LSG1 could be regulated by METTL14. Lnc-LSG1 can directly bind to ESRP2 protein and promote ESRP2 degradation via facilitating ESRP2 ubiquitination. However, m6A modification on Lnc-LSG1 can block the interaction between Lnc-LSG1 and ESRP2 via the m6A reader, YTHDC1. Taken together, our findings unraveled the novel mechanism of METTL14 inhibiting ccRCC progression, and explored the correlation between m6A and lncRNA in ccRCC for the first time.

[Application of imine covalent organic frameworks in sample pretreatment].

Imine covalent organic frameworks (I-COFs), including imine-linked COFs and hydrazone-linked COFs, are a new type of crystalline porous organic materials constructed by the condensation of organic monomers by the Schiff-base reaction. Because they are composed of lightweight elements linked by strong covalent bonds, I-COF materials possess the advantages of low skeleton density, large surface area, high porosity, abundant monomer species, controllable pore size, functionalized structure, diverse synthetic methods, excellent adsorption performance, outstanding physical and chemical stabilities, etc. In recent years, interest in the field of I-COFs has increased tremendously because of their exceptional performance and broad applications in gas storage, gas separation, catalysis, sensing, photoelectric materials, sample pretreatment, drug delivery, and other fields. To date, imine bonds are one of the most widely used covalent bonds in COFs, and represent one of the most important ways to obtain I-COFs with excellent chemical stabilities. The synthesis methods for I-COFs include solvothermal synthesis, microwave synthesis, mechanochemical grinding synthesis, and room-temperature synthesis methods. Solvothermal synthesis is the most extensively used method for the production of I-COFs with high specific surface areas and good thermal stabilities. The microwave synthesis method is conducive to the rapid synthesis of COFs in industry, providing a more time-saving, simpler, and safer route for large-scale preparation of I-COFs. The mechanochemical grinding synthesis of porous solids has gained importance as an alternative to conventional solvothermal synthesis, because the process is quick, environment-friendly, and potentially scalable. The room-temperature method is characterized by mild reaction conditions and rapid reactions. It is an energy-saving, economic, safe, and green synthesis method, which has emerged as a hot spot in the preparation of I-COFs in recent years. Research progress over the past years on the application of I-COFs in the field of materials science has undoubtedly established the basis of its application in analytical chemistry. Owing to the excellent physical and chemical properties of I-COF materials, they are suitable for use as separation and enrichment media for trace target compounds in complex samples. The high specific surface area and porosity, extended conjugate network skeleton, and π-electron-rich nature of the materials endow it with a high adsorption capacity. These materials are highly enriched in target analytes by π-π interactions, acid-base interactions, donor-acceptor interactions, hydrogen bonding, hydrophobic interactions, and other intermolecular interactions. Precise control of the microporous structure of I-COFs was obtained by controlling the chain length, geometric structure, doping elements, and substituent groups of the organic monomers. Selective enrichment of target trace substances was achieved by modifying the groups of I-COFs based on the principle of host guest adaptation, molecular sieving, or microporous filling effect. At present, research on the synthesis of I-COF materials is in the stage of rapid development, and many I-COFs with excellent properties and great application potential have been synthesized, allowing widespread application of I-COFs in sample pretreatment medium. This review summarizes the current state-of-the-art on the main types and synthetic methods of I-COFs, as well as the applications of I-COFs in solid-phase extraction, magnetic solid-phase extraction, dispersive solid-phase extraction, and solid-phase microextraction. The prospects of I-COFs in sample pretreatment are also presented.

A novel hydrogel orthotopic injection model in moderately hypofractionated radiation therapy for prostate cancer: Adaptive degradation and durable imaging.

Purpose: Moderately hypofractionated radiotherapy (MHRT) holds an important position in prostate cancer management. Existing hydrogel spacers can protect the rectum from radiation damage, but need improvement. We explored the application of a novel hydrogel in MHRT with adaptive degradation and durable imaging functions. Methods and materials: The hydrogels were irradiated with 6MV x-ray to detect the radio-resistance property. Male SD rats (n=45) underwent hydrogel injection between the prostate and rectum. CT was used for investigating the novel spacer's degradation and imaging functions over three months. The hydrogel's radiation-attenuation properties and biocompatibility were further assessed. Results: Hydrogel weight and volume remained stable for six weeks post-injection. After MHRT ended, the hydrogel showed accelerated degradation characteristics and remained in the body for at most three months. CT values of hydrogels exceeded 300 Hounsfield units (HU) throughout treatment, significantly higher than in surrounding normal tissues. A significant dose drop behind the hydrogel was observed post-implantation. Biocompatibility tests of hydrogel found it safe enough for living organisms. Conclusions: The novel hydrogel application was fully adaptable to prostate cancer MHRT modalities, largely stable during treatment, rapidly degraded after radiotherapy ended, and consistently maintained superior imaging performance and biocompatibility. This novel spacer will be an effective tool in the era of hypofractionated radiotherapy.

PIWI-interacting RNA 57125 restrains clear cell renal cell carcinoma metastasis by downregulating CCL3 expression.

Clear-cell renal cell carcinoma is one of the most common tumors disagnosed, with nearly one third of patients diagnosed with metastatic ccRCC. Although an increasing number of studies has revealed that piwi-interacting RNAs are aberrantly expressed in diverse types of cancers, few of them explored the detailed molecular mechanism of piRNAs in carcinogenesis, particularly in ccRCC. In this study, differentially expressed piRNAs associated with ccRCC were selected by using piRNA-sequencing combined with TCGA data analysis, and piR-57125 was identified. PiR-57125 was found remarkably downregulated in ccRCC samples. Functionally, knockdown of piR-57125 promoted migration and invasion of ccRCC, while overexpression of piR-57125 suppressed ccRCC metastasis. In vivo lung metastasis model also confirmed the same results. CCL3 was identified as the direct target of piR-57125 which could potentially reverse the inhibition effect of piR-57125 in ccRCC metastasis. Further study revealed that piR-57125 modulated ccRCC metastasis through the AKT/ERK pathway. These data indicate that piR-57125 restrains ccRCC metastasis by directly targeting CCL3 and inhibiting the AKT/ERK pathway, and could be a potential therapeutic target for ccRCC.

Quantitative global proteome and phosphorylome analyses reveal potential biomarkers in kidney cancer.

Currently, high­throughput quantitative proteomic and transcriptomic approaches have been widely used for exploring the molecular mechanisms and acquiring biomarkers for cancers. Our study aimed to illuminate the multi-dimensional molecular mechanisms underlying renal cell carcinoma (RCC) via investigating the quantitative global proteome and the profile of phosphorylation. A total of 5,428 proteins and 8,632 phosphorylation sites were quantified in RCC tissues, with 709 proteins and 649 phosphorylation sites found to be altered in expression compared with the matched adjacent non­tumor tissues. These differentially expressed proteins were mainly involved in metabolic process terms involving the glycolysis pathway, oxidative phosphorylation and fatty acid metabolism which have been considered to be a potential mechanism of RCC progression. Moreover, phosphorylation analysis indicated that these upregulated phosphorylated proteins are implicated in the glucagon signaling pathway and cholesterol metabolism, while the downregulated phosphorylated proteins were found to be predominantly involved in glycolysis, the pentose phosphate pathway, carbon metabolism and biosynthesis of amino acids. In addition, several new candidate proteins, CD14, MPO, NCF2, SOD2, PARP1, were found to be upregulated and MUT, ACADM, PCK1 were downregulated in RCC. These proteins may be recognized as new biomarkers for RCC. These findings could broaden our insight into the underlying molecular mechanisms of RCC and identify candidate biomarkers for the treatment of RCC.